Spinal and joint pain can be difficult to treat. In particular the cause of spinal and joint pain can be difficult to identify. Increasing degrees of force applied to joints result in joint injury. Abnormal joint anatomy is frequently a hallmark of ageing, but joint injury is also frequently seen as a result of trauma. For instance, chondral lesions are often seen in athletes. While joint injury resulting from trauma is typically associated with acute inflammation, aberrant joint anatomy resulting from ageing (e.g., osteoarthritis) is a chronic condition. Physicians currently do not have a system or method available to differentiate between acute injury due to trauma and age related joint deteriorations. It is presently difficult to determine the appropriate course of treatment for a given patient since it is frequently unclear whether the particular condition the patient suffers from is acute or chronic.
The exceedingly high rate of exploratory knee arthroscopy highlights the difficulty of diagnosing meniscal injury. This problem is exacerbated by the low specificity of MRI, currently a mainstay of diagnosing this pathology. It has been shown that MRI will identify a meniscal injury in as many as 65% of asymptomatic people making MRI a questionable diagnostic tool and highlighting the lack of correlation between abnormal meniscal anatomy and knee pain. Lack of a clear correlation between abnormal meniscus anatomy and knee pain is particularly problematic in the elderly patient population many of whom develop osteoarthritis. Despite the overwhelming evidence questioning its utility (Moseley, et al., N. Engl. J. Med., 347(2):81-8 (2002)), knee arthroscopy is still performed an estimated 660,000 times per year in the U.S. alone (AAOS website).
Spinal-related pain is typically classified as discogenic, facetogenic or radiculopathic pain. The manifestation of radiculopathic pain has traditionally been attributed to various physical/mechanical abnormalities, such as compression or mechanical irritation of the nerve root related to conditions such as disk herniation, stenosis, spondylolisthesis, sciatica, Piriformis Syndrome, Obturator Syndrome, cystic lesions (e.g., ganglion and synovial), tumors, and other pathology.
It has been demonstrated that the application of nucleus pulposus to the spinal nerve root can result in axonal damage and functional changes to nerve root micro-anatomy, resulting in pain-related behaviors. Thus, it has been theorized that a mechanical defect releasing the nucleus pulposus into the epidural space may cause nerve root damage resulting in radicular pain. This “chemical radiculopathy” may explain the presence of radiculopathic pain in only a portion of a patient population that has mechanical failures such as disk herniation, while the remaining patients remain pain-free.
Numerous studies have attempted to elucidate the pathophysiology of spinal-related pain, and several molecular pathways have been implicated tentatively. However, no clear causal pathway leading from injury or degeneration to the painful state has been confirmed. Molecular markers may be linked to clinical symptoms, and serve as potential targets for the development of diagnostics and therapeutic tools. Although some studies have provided evidence that the epidural space may be affected by an intervertebral disk herniation, none has measured concentrations of biomolecules in the epidural space in an attempt to detect the differences between affected and non-affected persons.
Therefore, it is an object of the invention to provide biomarkers that are indicative of pain in the spine or joint.
It is another object of the invention to provide biomarkers and methods for identifying sites in the spine or joint for treating pain.
It is another object of the invention to provide biomarkers that may be used to diagnose or assist in the diagnosis of the presence of pathologies that are causative of spinal- or joint-related pain.
It is another object of the invention to provide methods for diagnosing or assisting in the diagnosis of the presence of pathologies that are causative of spinal- or joint-related related pain.
It is yet another object of the invention to provide biomarkers and methods to determine an appropriate therapy for a subject experiencing spinal- or joint-related pain.
It is yet another object of the invention to provide biomarkers and methods to monitor and assess the efficacy of a treatment for spinal- or joint-related pain.
It is still another object of the invention to provide compositions and methods for treating spinal or joint pain.
It is still another object to provide methods and compositions for selecting treatment sites in the spine or joint for treatment to inhibit or reduce pain.